FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
PURIFICATION PROCESS FOR (E)-N,N-DIETHYL-2-CYANO-3-(3,4-DIHYDROXY-5-NITROPHENYL)ACRYLAMIDE
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Limited, D-4, MIDC, Chikalthana,
Aurangabad (M.S.) INDIA.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a purification process for ( E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention provides a purification process for ( E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.
Entacapone of formula I, chemically known as (E)-N, N-Diethyl-2- cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide. It is indicated for the treatment of Parkinson's disease.

British patent No. 8,727,854 describes entacapone as a potent inhibitor of catechol-O-methyl- transferase (COMT) enzyme.
US Patent 4,963,590 discloses a process for the preparation of entacapone (Formula I) by the condensation of 3,4-Dihydroxy-5- nitrobenzaldehyde and N,N-diethylcyanoacetamide in anhydrous ethanol.
US Patent 5,135,950 discloses crystallographically essentially pure and stable polymorphic form A of entacapone.
The processes of preparation of entacapone and different polymorphic forms are also disclosed in PCT patent application WO 2005063693; WO 2005063695; WO 2005063696; WO 2005066117 and WO 200507088.
The inventors have surprisingly found that entacapone contaminated by impurity such as 3,4-dihydroxy-5-nitrobenzaldehyde, 2-cyno-N,N-diethyl acetamide and

(Z) entacapone, wherein the level of these impurities is more than 0.5% can be purified by suspending the entacapone in organic acid and purified entacapone can be directly isolated from the reaction mass, having purity 99.6% or more when measured by HPLC.
The crude entacapone refers to entacapone having 3, 4-dihydroxy-5-nitrobenzaldehyde, 2-cyno-N,N-diethyl acetamide and (Z) entacapone as an impurities and level of theses impurities are more than 0.5%, and purity of entacapone is 98% or less.
In the aspect of present invention there is provided a process for the purification of entacapone, wherein the said process includes steps of,
a) treating entacapone with an organic acid,
b) isolating the pure entacapone from reaction mass thereof.
The Process of present invention involves suspending crude entacapone in an organic acid such as acetic acid and formic acid and heated. The purified product is isolated after cooling of reaction mass to below to 35°C. The purified entacapone obtained by this process is having the purity 99.9% and substantially free from any impurity when measured by HPLC.
The term substantially free from impurities refer as no impurity is more than 0.05% present in entacapone.
The present invention is further illustrated by the following example which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Example Purification of (E)-N, N-Diethyl-2-cyano-3-(3, 4-dihydroxy-5-nitrophenyl) acrylamide (Entacapone)
The Crude entacapone (100 gm) was charged with acetic acid (250 ml), The
reaction mass was heated at 60°C for 1 hours and the cooled to 25°C. The
reaction mass was further stirred for 2hours. The solid was filtered and washed
with water (250ml). The product was dried to get the (E)-N, N-Diethyl-2-cyano-3-
(3, 4-dihydroxy-5-nitrophenyl) acrylamide.
Yield: 90 gm.
HPLC Purity: 99.96%.
3, 4-dihydroxy-5-nitrobenzaldehyde: 0.01 %
2-cyano -N, N-diethyl acetamide: ND
(Z)-Entacapone 0.02%

WE CLAIM:
1. A process for the purification of entacapone, wherein the said process
comprises of,
a) treating entacapone with an organic acid,
b) isolating the pure entacapone of from reaction mass thereof.

2. The process of claim 1 wherein the organic acid is selected from acetic acid or formic acid.
3. The process of claim 1, wherein pure entacapone having purity is 99.5% or more.
4. The process of claim 3, wherein purity is 99.9% when measured by HPLC.

Abstract
The present invention provides a purification process for ( E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.